Synthesis, characterization and in vitro anti-proliferative effects of pentacyclic triterpenoids

: Bladder cancer carries a poor prognosis and has proven resistance to chemotherapy. Pentacyclic Triterpenoid Acids (PTAs) are natural bioactive compounds that have a well-known impact on cancer research because of their cytotoxic and chemopreventive activities. This review focuses on bladder cancer which can no longer be successfully treated by DNA damaging drugs. Unlike most of the existing drugs against bladder cancer, PTAs are non-toxic to normal cells. Collecting findings from both in vitro and in vivo studies, it has been concluded that PTAs may serve as promising agents in future bladder cancer therapy. In this review, the roles of various PTAs in bladder cancer have been explored, and their mechanisms of action in the treatment of bladder cancer have been described. Specific PTAs have been shortlisted from each of the chief skeletons of pentacyclic triterpenoids, which could be effective against bladder cancer because of their mode of action. This review thereby throws light on the multi targets and mechanisms of PTAs, which are responsible for their selective anticancer effects and provides guidelines for further research and development of new natural antitumor compounds.

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Cytotoxic Pentacyclic Triterpenoids from Combretum oliviforme

Natural Product Communications ◽

10.1177/1934578x1000500708 ◽

2010 ◽

Vol 5 (7) ◽

pp. 1934578X1000500

Author(s):

Xiao-Peng Wu ◽

Chang-Ri Han ◽

Guang-Ying Chen ◽

Yuan Yuan ◽

Jian-Ying Xie

Keyword(s):

Cytotoxic Activity ◽

Cancer Cell Line ◽

Lung Cancer Cell Line ◽

Human Lung Cancer ◽

Ionization Mass ◽

Human Gastric Cancer ◽

Pentacyclic Triterpenoids ◽

Acetyl Group ◽

First Time

Four pentacyclic triterpenoids were obtained from the leaves of Combretum oliviforme Chao, 3β–hydroxyolean–12–en–28–oic acid (1), 23– O–[α-L-(4′-acetylrhamnopyranosyl)]–imberbic acid (2), 23–acetoxy–3β–acetylimberbic acid–29–methyl ester (3), and 23– O–[α-L-rhamnopyranosyl]-1,3β-diacetylimberbic acid (4). Hydrolysis of 2 and 4 gave 23–hydroxyimberbic acid (5). The structures were elucidated by NMR, electrospray ionization mass spectrometry (ESIMS) and comparison with literature data. Compounds 1, 2, 3 and 4 were isolated from C. oliviforme Chao leaves for the first time and 3 for the first time from any natural source. All compounds were tested in vitro for their activity against human lung cancer cell line SPC-A-1, human erythroleukaemic line K562 and human gastric cancer SGC-7901 cells. Compounds 1, 3, 4 and 5 had cytotoxic activity for the three cell lines with IC50 0.69-69.68 μM. These results suggest that the presence of acetyl group in the triterpene aglycone structure plays an essential role for cytotoxic activity.

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Pentacyclic triterpenoids from Mitracarpus frigidus (Willd. ex Roem. & Schult.) K. Shum: in vitro cytotoxic and leishmanicidal and in vivo anti-inflammatory and antioxidative activities

Medicinal Chemistry Research ◽

10.1007/s00044-014-1093-y ◽

2014 ◽

Vol 23 (12) ◽

pp. 5294-5304 ◽

Cited By ~ 8

Author(s):

Rodrigo Luiz Fabri ◽

Roberta Alvim Garcia ◽

Jônatas Rodrigues Florêncio ◽

Lidiane Oliveira de Carvalho ◽

Nícolas de Castro Campos Pinto ◽

...

Keyword(s):

Pentacyclic Triterpenoids ◽

Anti Inflammatory

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In vitro propagation, genetic and phytochemical assessment of Thymus persicus — a medicinally important source of pentacyclic triterpenoids

Biologia ◽

10.2478/s11756-014-0346-z ◽

2014 ◽

Vol 69 (5) ◽

Cited By ~ 17

Author(s):

Ziba Bakhtiar ◽

Mohammad Mirjalili ◽

Ali Sonboli ◽

Mahdi Farimani ◽

Mahdi Ayyari

Keyword(s):

Acetic Acid ◽

High Performance ◽

In Vitro Propagation ◽

Random Amplified Polymorphic Dna ◽

Direct Organogenesis ◽

Naphthalene Acetic Acid ◽

Ms Medium ◽

Pentacyclic Triterpenoids ◽

Thymus Persicus

AbstractThymus persicus (Ronniger ex Rech. f.) Jalas is a valuable and endangered natural source of antitumor pentacyclic triterpenoids, i.e., betulinic acid, oleanolic acid and ursolic acid, which grows in northwest Iran. As the plant has a low propagation rate in nature, a suitable method for in vitro-propagation is needed. With the aim of identifying a suitable system for regenerating T. persicus via direct organogenesis, Murashige & Skoog (MS) medium supplemented with different plant growth regulators (PGRs) was tested. In vitro-grown shoot tips were exposed to the cytokinins 6-benzylaminopurine (BAP), kinetin (KN), and thidiazuron (TDZ), alone or in combination with the auxins 1-naphthalene-acetic acid (NAA), 2,4-dichlorophenoxyacetic (2,4-D), indole-3-butyric acid (IBA) and indole-3-acetic acid (IAA). The highest shoot formation (7.1 ± 0.9) was obtained with a medium fortified with 8.9 μM BAP plus 2.7 μM NAA. Regenerated shoots were easily rooted on the different tested media, with the most abundant (16.6 ± 1.4) and strongest roots obtained on half-strength MS medium containing 2.5 μM IBA. The rooted plantlets were successfully acclimatized (76.6%) in a greenhouse before transference to natural conditions. Homogeneity and phytochemical productivity of the in vitro regenerated plantlets were confirmed by random amplified polymorphic DNA (RAPD) profiles and high performance liquid chromatography (HPLC), respectively.

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Ursolic and Oleanolic Acids as Potential Anticancer Agents Acting in the Gastrointestinal Tract

Mini-Reviews in Organic Chemistry ◽

10.2174/1570193x15666180612090816 ◽

2018 ◽

Vol 16 (1) ◽

pp. 78-91 ◽

Cited By ~ 5

Author(s):

Mateusz Pięt ◽

Roman Paduch

Keyword(s):

Gastrointestinal Tract ◽

Side Effects ◽

Anticancer Agents ◽

In Vivo Studies ◽

Pentacyclic Triterpenoids ◽

Liver Cancers ◽

Anti Cancer ◽

Tumorigenic Activity

Background:Cancer is one of the main causes of death worldwide. Contemporary therapies, including chemo- and radiotherapy, are burdened with severe side effects. Thus, there exists an urgent need to develop therapies that would be less devastating to the patient’s body. Such novel approaches can be based on the anti-tumorigenic activity of particular compounds or may involve sensitizing cells to chemotherapy and radiotherapy or reducing the side-effects of regular treatment.Objective:Natural-derived compounds are becoming more and more popular in cancer research. Examples of such substances are Ursolic Acid (UA) and Oleanolic Acid (OA), plant-derived pentacyclic triterpenoids which possess numerous beneficial properties, including anti-tumorigenic activity.Results:In recent years, ursolic and oleanolic acids have been demonstrated to exert a range of anticancer effects on various types of tumors. These compounds inhibit the viability and proliferation of cancer cells, prevent their migration and metastasis and induce their apoptosis. Both in vitro and in vivo studies indicate that UA and OA are promising anti-cancer agents that can prevent carcinogenesis at each step. Furthermore, cancers at all stages are susceptible to the activity of these compounds. </P><P> Neoplasms that are formed in the gastrointestinal tract, i.e. gastric, colorectal, pancreatic, and liver cancers, are among the most common and most lethal malignancies. Their localization in the digestive system, however, facilitates the action of orally-administered (potential) anti-cancer agents, making chemopreventive drugs more accessible.In this paper, the anti-tumorigenic effect of ursolic and oleanolic acids on gastric, colon, pancreatic, and liver cancers, as well as the mechanisms underlying this process, are presented.

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In Vitro Production and Exudation of 20-Hydroxymaytenin from Gymnosporia heterophylla (Eckl. and Zeyh.) Loes. Cell Culture

Plants ◽

10.3390/plants10081493 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1493

Author(s):

Thanet Pitakbut ◽

Michael Spiteller ◽

Oliver Kayser

Keyword(s):

Biological Activities ◽

Quinone Methide ◽

Induction Medium ◽

Naphthalene Acetic Acid ◽

In Vitro Production ◽

Pentacyclic Triterpenoids ◽

Anticancer Properties ◽

Vitro Production ◽

First Time

The metabolite 20-Hydroxymaytenin (20-HM) is a member of the quinone-methide pentacyclic triterpenoids (QMTs) group. This metabolite group is present only in Celastraceae plants, and it has shown various biological activities from antioxidant to anticancer properties. However, most QMTs metabolites including 20-HM cannot be synthesized in a laboratory. Therefore, we optimized a plant tissue culture protocol and examined the potential of Gymnosporia heterophylla (synonym. Maytenus heterophylla) to produce 20-HM in an in vitro experiment. For the first time, we reported the optimum callus induction medium with a high percentage success rate of 82% from the combination of 1 mg/L indole-3-butyric acid and 5 mg/L naphthalene acetic acid. Later, our cell suspension culture cultivated in the optimum medium provided approximately 0.35 mg/g fresh weight of 20-HM. This concentration is roughly 87.5 times higher than a concentration of 20-HM presenting in Elaeodendron croceum (Celastraceae) leaves. In addition, we also found that 20-HM presented in a cultivation medium, suggesting that G. heterophylla cells secreted 20-HM as an exudate in our experiment. Noticeably, 20-HM was missing when Penicillium cf. olsonii occurred in the medium. These findings hint at an antifungal property of 20-HM.

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Pentacyclic Triterpenoids Inhibit IKKβ Mediated Activation of NF-κB Pathway: In Silico and In Vitro Evidences

PLoS ONE ◽

10.1371/journal.pone.0125709 ◽

2015 ◽

Vol 10 (5) ◽

pp. e0125709 ◽

Cited By ~ 27

Author(s):

Kalpesh R. Patil ◽

Purusottam Mohapatra ◽

Harun M. Patel ◽

Sameer N. Goyal ◽

Shreesh Ojha ◽

...

Keyword(s):

In Silico ◽

Pentacyclic Triterpenoids

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Synthesis, Characterization, In Vitro Anticancer Potentiality, and Antimicrobial Activities of Novel Peptide–Glycyrrhetinic-Acid-Based Derivatives

Molecules ◽

10.3390/molecules26154573 ◽

2021 ◽

Vol 26 (15) ◽

pp. 4573

Author(s):

Gaber O. Moustafa ◽

Ahmed Shalaby ◽

Ahmed M. Naglah ◽

Marwa M. Mounier ◽

Heba El-Sayed ◽

...

Keyword(s):

Cytotoxic Activity ◽

Cell Line ◽

Cancer Cell ◽

Micrococcus Luteus ◽

Normal Skin ◽

Cancer Cell Line ◽

Glycyrrhetinic Acid ◽

Pentacyclic Triterpenoids ◽

Vitro Effect

Glycyrrhetinic acid (GA) is one of many interesting pentacyclic triterpenoids showing significant anticancer activity by triggering apoptosis in tumor cell lines. This study deals with the design and synthesis of new glycyrrhetinic acid (GA)–amino acid peptides and peptide ester derivatives. The structures of the new derivatives were established through various spectral and microanalytical data. The novel compounds were screened for their in vitro cytotoxic activity. The evaluation results showed that the new peptides produced promising cytotoxic activity against the human breast MCF-7 cancer cell line while comparing to doxorubicin. On the other hand, only compounds 3, 5, and 7 produced potent activity against human colon HCT-116 cancer cell line. The human liver cancer (HepG-2) cell line represented a higher sensitivity to peptide 7 (IC50; 3.30 μg/mL), while it appeared insensitive to the rest of the tested peptides. Furthermore, compounds 1, 3, and 5 exhibited a promising safety profile against human normal skin fibroblasts cell line BJ-1. In order to investigate the mode of action, compound 5 was selected as a representative example to study its in vitro effect against the apoptotic parameters and Bax/BCL-2/p53/caspase-7/caspase-3/tubulin, and DNA fragmentation to investigate beta (TUBb). Additionally, all the new analogues were subjected to antimicrobial assay against a panel of Gram-positive and Gram-negative bacteria and the yeast candida Albicans. All the tested GA analogues 1–8 exhibited more antibacterial effect against Micrococcus Luteus than gentamicin, but they exhibited moderate antimicrobial activity against the tested bacterial and yeast strains. Molecular docking studies were also simulated for compound 5 to give better rationalization and put insight to the features of its structure.

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The Effect of Oleanolic and Ursolic Acids on the Hemolytic Properties and Biofilm Formation of Listeria monocytogenes

Polish Journal of Microbiology ◽

10.33073/pjm-2014-003 ◽

2014 ◽

Vol 63 (1) ◽

pp. 21-25 ◽

Cited By ~ 6

Author(s):

ANNA KUREK ◽

KATARZYNA MARKOWSKA ◽

ANNA M. GRUDNIAK ◽

WIRGINIA JANISZOWSKA ◽

KRYSTYNA I. WOLSKA

Keyword(s):

Antibacterial Activity ◽

Listeria Monocytogenes ◽

Medicinal Plants ◽

Oleanolic Acid ◽

Biofilm Formation ◽

Listeriolysin O ◽

Pentacyclic Triterpenoids ◽

Toxin Secretion ◽

Vitro Effect

Oleanolic acid and ursolic acid are pentacyclic triterpenoids isolated from a variety of medicinal plants, which have antibacterial activity. Listeria monocytogenes is a Gram-positive facultative pathogen, being the causative agent of listeriosis. The present study was carried out to evaluate the in vitro effect of sub-inhibitory concentrations of both triterpene acids on the pathogenicity determinants of L. monocytogenes: their hemolytic activity and biofilm forming ability. Oleanolic and ursolic acids inhibited listeriolysin O activity without influencing toxin secretion. Biofilm formation, and the viability of L. monocytogenes cells in biofilms was diminished by both compounds. Thus, both acids affected L. monocytogenes virulence. It was also demonstrated that oleanolic acid bound to the peptidoglycan of L. monocytogenes and this interaction was influenced by teichoic acids.

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